Case Discussion <Case report> An 18-year-old Chinese woman was evaluated for an episode of sudden collapse. The episode happened during a trip of outdoor teaching. She lost her consciousness suddenly when bending down to wear her shoes. She was resuscitated by local medical personnel in an ambulance and was sent to emergence service immediately. The ambulatory electrocardiogram (ECG) recorded by automatic external defibrillator revealed polymorphic and bidirectional VT (figure 1 ). She fully recovered after the resuscitation. She was healthy and had never experienced syncope or exercise-induced dizziness before. There was no history of heart disease, syncope, and sudden death in her family. Her blood pressure was 132/68 mmHg and her respiratory rate was 22/min. There was no lymph node enlargement or jugular vein engorgment on the neck. Her breath sounds were clear. The heart sounds were regular without murmur. The abdomen was soft with normoactive bowel sounds. The extremities were freely movable without significant edema or cyanosis. Laboratory tests including biochemical profile and serum electrolytes were unremarkable (table 1). The electrocardiogram (figure 2 ), signal average electrocardiogram, transthoracic echocardiography, and magnetic resonance imaging were also within normal limit. In order to evaluate the possibility of exercise-induced arrhythmia, she underwent a treadmill exercise test. After one minute of exercise, short runs of bidirectional and polymorphic ventricular tachycardia developed. Ventricular tachycardia became sustained and bidirectional within next two minutes (figure 3 ). Exercise was stopped and ventricular tachycardia terminated 4 minutes later. She remained free of symptoms and hemodynamically stable throughout the exercise test. Programmed electrical stimulation failed to induce sustained or nonsustained ventricular tachycardia and so did isoprotenolol infusion. The procainamide provocation test was negative, so that Brugada syndrome was excluded. She was diagnosed with catecholaminergic polymorphic ventricular tachycardia (CPVT), and was placed on long-term treatment with a β-blocker. Implantation of an automatic internal cardioverter defibrillator was suggested, but she refused. She was free of symptoms at six-month follow-up. <Discussion> Exercise-induced ventricular tachycardia in children and young adult without structural heart disease are rare. Generally, the prognosis is relative benign if the morphology is monomorphic [1]. CPVT is a special entity with multiform morphology carrying a worse prognosis [1,2]. Most cases of CPVT are reported among Caucasian and Japanese. However, CPVT is never reported among Taiwanese. The definition of CPVT includes several factors. First, more than two type of ventricular tachycardia morphology can be induced by exercise or catecholamine infusion during more than three consecutive beats. Second, there is absence of electrolyte imbalance, drug treatment, or organic heart disease. Finally, there is absence of primary electrical disease such as long QT syndrome or Brugada syndrome [1]. The morphology of CPVT is polymorphic, bidirectional, ventricular fibrillation, or their combination [1,3]. Fourteen percent of patients with CPVT had a positive family history [1]. Recent studies suggest that familial CPVT is a genetic disorder. Both autosomal dominant and autosomal recessive forms are found in genetic inheritance. Lineage analysis reveal that a locus at 1q42-q43 is associated with CPVT with an autosomal dominant inheritance [4]. Further analysis show that cardiac ryanodine receptor gene (RyR2) is the disease causing gene [5]. In patients with an autosomal recessive inheritance, the disease locus is located at 1q31-21 and the responsible gene is cardiac calsequestrin (CASQ2) [6]. Both pattern of mutation are associated with increased calcium release from the sarcoplasmic reticulum. The prognosis of CPVT is poor. Mortality rate is around 30% by the age of 30 [4,5]. β-blocker is effective in deceasing the attacks. However, it completely controls CPVT in only one-third of patients [1]. Implantation of an implantable cardioverter defibrillator is indicated in patients who are at high risk or have recurrent attacks even under β-blocker therapy. Table 1. Laboratory data [ CBC+PLT ]   WBC  RBC Hct Hb  MCV MCHC  PLT Unit K/μL M/μL %  g/dL  fL g/dL K /μL Value 7.86 4.39 38.4 12.9 87.5 33.6 467.0 [ Biochemistry ]   T-bil Alb AST ALP BUN Cre Unit mg/dL g/dL U/L  U/I mg/dL mg/dL Value 0.29 4.37 35 204.0 9.0 0.5   Na K Ca Mg Unit mmol/l mmol/l mmol/l mmol/l Value 140.3 4.3 2.39 0.87 [ Coagulation profile] PT/PT, control 13.2/12.4, INR:1.1 PTT/PTT control 37.1/35.9 [ Serology ] C-reactive protein: 0.45 mg/dl Legend of figure figure 1 : The long strip of the electrocardiogram in a external defibrillator reveals intermittently alternating bidirectional and polymorphic ventricular tachycardia. figure 2 : The resting electrocardiogram is morphological normal and no QT prolongation was noted. figure 3 : The exercise electrocardiogram in third minute of exertional time reveals sustained bidirectional ventricular tachycardia. <Reference > 1. Sumitomo N, Harada K, Nagashima M, et al. Catecholaminergic polymorphic ventricular tachycardia: electrocardiographic characteristics and optimal therapeutic strategies to prevent sudden death. Heart 2003;89:66-70. 2. Leenhardt A, Lucet V, Denjoy I, Grau F, Ngoc DD, Coumel P. Catecholaminergic polymorphic ventricular tachycardia in children: A 7-year follow-up of 21 patients. Circulation 1995;91:1512-1519. 3. Swan H, Piippo K, Viitasalo M, et al. Arrhythmic disorder mapped to chromosome 1q42-q43 causes malignant polymorphic ventricular tachycardia in structurally normal hearts. J Am Coll Cadiol 1999;34:2035-42. 4. Priori SG, Napolitano C, Memmi M, et al. Clinical and molecular characterization of patients with catecholaminergic polymorphic ventricular tachycardia. Circulation 2002;106:69-74. 5. Laitinen P, Brown KM, Piipo K, et al. Mutation of the cardiac ryanodine receptor (RyR2) gene in familial polymorphic ventricular tachycardia. Circulation 2001;103:485-490. 6. Lahat H, Pras E, Olender T, et al. A missense mutation in a highly conserved region of CASQ2 is associated with autosomal recessive catecholamine-induced polymorphic ventricular tachycardia in Bedouin families from Israel. Am J Hum Genet 2001;69:1378-1384. 繼續教育考題 1. (D) What are the possible causes of exercise-induced ventricular tachycardia? A myocardial scar due to myocardial infarction B Congenital long-QT syndrome C CPVT D all of above 2. (C) What are the possible causes of bidirectional ventricular tachycardia? A digoxin intoxication B catecholaminergic polymorphic ventricular tachycardia (CPVT) C both D neither. 3. (D) What factor is not necessary for the definition of CPVT? A more than two type of ventricular tachycardia morphology can be induced by exercise or catecholamine infusion B absence of electrolyte imbalance, drug treatment, or organic heart disease C absence of primary electrical disease D history of sudden cardiac death. 4. (D) The ECG morphology of CPVT can be A polymorphic B bidirectional C ventricular fibrillation D all of above. 5. (C) What is the hereditary pattern of familial CPVT? A Autosomal dominant B Autosomal recessive C both D neither. 6. (C) What is the possible gene of familial CPVT? A cardiac ryanodine receptor gene (RyR2) B cardiac calsequestrin (CASQ2) C both D neither. 7. (D) What kind of electrolyte is associated with familial CPVT? A Na B K C Mg D Ca 8. (B) What is the mortality rate of CPVT patients by the age of 30? A 10% B 30% C 50% D 70% 9. (A) What is the suitable pharmalogocal therapy for CPVT?  A β-blocker B amiodarone C quinidine D lidocaine 10. (B) What is the best treatment for this patient? A β-blocker only B  implantable cardioverter defibrillator C quinidine D  lidocaine 答案解說 (D) All of these three disease cause exercise-induced ventricular tachycardia. (C) Both digoxin intoxication and CPVT cause bidirectional VT (D) The definition of CPVT includes several factors. First, more than two type of ventricular tachycardia morphology can be induced by exercise or catecholamine infusion during more than three consecutive beats. Second, there is absence of electrolyte imbalance, drug treatment, or organic heart disease. Finally, there is absence of primary electrical disease such as long QT syndrome or the Brugada's syndrome. (D) The morphology of CPVT is polymorphic, bidirectional, ventricular fibrillation, or their combination. (C) Both autosomal dominant and autosomal recessive forms are found in genetic inheritance. (C) Lineage analysis revealed that a locus at 1q42-q43 is associated with CPVT with an autosomal dominant inheritance. Further analysis show that cardiac ryanodine receptor gene (RyR2) is the disease causing gene. In patients with an autosomal recessive inheritance, the disease locus is located at 1q31-21 and the responsible gene is cardiac calsequestrin (CASQ2). (D) Familial CPVT is associated with increased calcium release from the sarcoplasmic reticulum. (B) Mortality rate of CPVT is around 30% by the age of 30. (A ) By far, β-blocker is most suitable pharmacological agent to control CPVT. (B) Implantation of an implantable cardioverter defibrillator is indicated in secondary prevention of CPVT patients and primary prevention in high risk CPVT patients.